In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 1 ( 2001-01-02), p. 119-124
Abstract:
Matrix metalloproteinase 2 (MMP2) can associate with
integrin α v β 3 on the surface of endothelial
cells, thereby promoting vascular invasion. Here, we describe an organic molecule (TSRI265) selected for its ability to bind to integrin
α v β 3 and block
α v β 3 interaction with MMP2. Although
disrupting α v β 3 /MMP2 complex formation,
TSRI265 has no effect on α v β 3 binding to
its extracellular matrix ligand vitronectin and does not influence MMP2 activation or catalytic activity directly. However, TSRI265 acts as a potent antiangiogenic agent and thereby blocks tumor growth in
vivo . These findings suggest that activated MMP2 does not
facilitate vascular invasion during angiogenesis unless it forms a complex with α v β 3 on the endothelial cell
surface. By disrupting endothelial cell invasion without broadly suppressing cell adhesion or MMP function, the use of compounds such as
TSRI265 may provide a novel therapeutic approach for diseases associated with uncontrolled angiogenesis.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.98.1.119
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2001
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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